Methods for treating epstein-barr virus (ebv) associated cancers using oral formulations of 5-azacytidine

Abstract

Provided herein are methods for treating subjects having an EBV-associated cancer, including a relapsed or refractory solid tumor and Burkitt's lymphoma, wherein the method comprises administering to the subject 5-azacytidine. In certain of the methods, 5-azacytidine is administered alone or in combination with one or more anti-cancer agents. In certain of the methods, 5-azacytidine is formulated in an oral dosage form and administered orally.

What is claimed is: 
     
         1 . A method for treating a subject having an EBV-associated cancer, wherein the method comprises orally administering to the subject a pharmaceutical composition comprising 5-azacytidine, or a pharmaceutically acceptable salt, solvate, or hydrate thereof; and the method optionally further comprises administering at least one additional therapeutic agent. 
     
     
         2 . The method of  claim 1 , wherein the EBV-associated cancer is a relapsed or refractory solid tumor. 
     
     
         3 . The method of  claim 1 , wherein the EBV-associated cancer is adenocarcinoma consistent with pancreatiocobiliary. 
     
     
         4 . The method of  claim 1 , wherein the EBV-associated cancer is lymphoma. 
     
     
         5 . The method of  claim 4 , wherein the lymphoma is Burkitt's lymphoma. 
     
     
         6 . The method of  claim 1 , wherein the additional therapeutic agent is an anti-cancer agent. 
     
     
         7 . The method of  claim 6 , wherein the additional therapeutic agent is a platinum agent. 
     
     
         8 . The method of  claim 7 , wherein the additional therapeutic agent is carboplatin. 
     
     
         9 . The method of  claim 6 , wherein the additional therapeutic agent is a taxane. 
     
     
         10 . The method of  claim 9 , wherein the additional therapeutic agent is paclitaxel. 
     
     
         11 . The method of  claim 9 , wherein the additional therapeutic agent is paclitaxel protein-bound particles. 
     
     
         12 . The method of  claim 9 , wherein the additional therapeutic agent is Abraxane. 
     
     
         13 . The method of  claim 1 , wherein the additional therapeutic agent is romidepsin. 
     
     
         14 . The method of  claim 1 , wherein the method comprises the steps of:
 (i) administering 5-azacytidine to the subject for 1, 2, 3, 4, 5, 6, or 7 days; and   (ii) administering the additional therapeutic agent to the subject for one or more days.   
     
     
         15 . The method of  claim 14 , wherein the additional therapeutic agent is administered parenterally. 
     
     
         16 . The method of  claim 14 , wherein the additional therapeutic agent is administered orally. 
     
     
         17 . The method of  claim 14 , wherein step (ii) further comprises administering 5-azacytidine orally for 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 days. 
     
     
         18 . The method of  claim 14 , wherein the method comprises the sequential steps of:
 (i) administering 5-azacytidine to the subject for 7 days;   (ii) administering the additional therapeutic agent to the subject for 1 day;   (iii) administering 5-azacytidine to the subject for 6 days; and   (iv) repeating steps (i) to (iii) after 7 days of resting period.   
     
     
         19 . The method of  claim 14 , wherein the method comprises the sequential steps of:
 (i) administering 5-azacytidine to the subject for 7 days;   (ii) administering 5-azacytidine and the additional therapeutic agent to the subject for 1 day;   (iii) administering 5-azacytidine to the subject for 6 days; and   (iv) repeating steps (i) to (iii) after 7 days of resting period.   
     
     
         20 . The method of  claim 14 , wherein the method comprises the sequential steps of:
 (i) administering 5-azacytidine to the subject for 7 days;   (ii) administering 5-azacytidine and the additional therapeutic agent to the subject for 1 day;   (iii) administering 5-azacytidine to the subject for 6 days;   (iv) administering the additional therapeutic agent to the subject for 1 day; and   (v) repeating steps (i) to (iv) after 6 days of resting period.   
     
     
         21 . The method of  claim 14 , wherein the method comprises the sequential steps of:
 (i) administering 5-azacytidine to the subject for 7 days;   (ii) administering 5-azacytidine and the additional therapeutic agent to the subject for 1 day;   (iii) administering 5-azacytidine to the subject for 6 days;   (iv) administering the additional therapeutic agent to the subject for 1 day;   (v) administering 5-azacytidine and the additional therapeutic agent to the subject for 1 day after 6 days of resting period;   (vi) administering 5-azacytidine to the subject for 6 days; and   (vii) repeating steps (ii) to (vi).   
     
     
         22 . The method of  claim 1 , wherein the method comprises administering 5-azacytidine to the subject for at least 1, at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 days, before administering the additional therapeutic agent to the subject. 
     
     
         23 . The method of  claim 22 , wherein the additional therapeutic agent is administered parenterally for one or more days. 
     
     
         24 . The method of  claim 22 , wherein the additional therapeutic agent is administered orally for one or more days. 
     
     
         25 . The method of  claim 1 , wherein the pharmaceutical composition comprising 5-azacytidine is a tablet. 
     
     
         26 . The method of  claim 1 , wherein the pharmaceutical composition comprising 5-azacytidine is a capsule. 
     
     
         27 . The method of  claim 1 , wherein the pharmaceutical composition comprises about 100 mg, about 200 mg, about 300 mg, about 400 mg, about 500 mg, or about 600 mg of 5-azacytidine. 
     
     
         28 . The method of  claim 1 , wherein the pharmaceutical composition comprises about 200 mg of 5-azacytidine. 
     
     
         29 . The method of  claim 1 , wherein the pharmaceutical composition comprises about 300 mg of 5-azacytidine. 
     
     
         30 . The method of  claim 1 , wherein the subject is a human.